Method for suturelessly attaching a biomaterial to an implantable bioprosthesis frame

ABSTRACT

A bioprosthetic valve graft comprises a valve frame and valve flaps, the latter acting to open or close a valve aperture to directionally control fluid flow through the bioprosthesis. The bioprosthetic valve graft comprises method for suturelessly attaching a biomaterial suturelessly bonded to the A method for securing a biomaterial to a valve frame includes positioning a flexible valve frame defining an open area on a first major surface of a biomaterial sheet having a peripheral edge, wherein positioning serves to approximate the valve frame and the peripheral edge of the biomaterial sheet to form an at least first bonding locus: and suturelessly bonding the biomaterial to the valve frame at the at least first bonding locus. The method avoids the disadvantages associated with conventional sutures and substantially reduces medical complications in implantations.

RELATED APPLICATION DATA

This application is a divisional of U.S. Ser. No. 10/104,499, filed onMarch 21, 2002.

STATEMENT OF GOVERNMENT RIGHTS

This invention was made with the U.S. Government support under GrantNumber DAMD17-96-1-6006, awarded by the Army Medical Research andMateriel Command. The U.S. Government may have certain rights in theinvention.

BACKGROUND OF THE INVENTION

The present disclosure is related to the field of artificial valves, andmore specifically to an implantable, sutureless valve graft comprising abiomaterial. The disclosure is further related to a method forsuturelessly bonding a biomaterial to a bioprosthetic frame.

Prosthetic stents and valves have been described in the prior art.Stents have been used with success to overcome the problems ofrestenosis or re-narrowing of a vessel wall. Valves are exemplified byU.S. Pat. No. 5,258,023 (to Roger), in which a prosthetic valve istaught that is constructed of synthetic materials.

However, the use of such devices is often associated with thrombosis andother complications. Additionally, prosthetic devices implanted invascular vessels can exacerbate underlying atherosclerosis.

Research has focused on trying to incorporate artificial materials orbiocompatible materials as bioprosthesis coverings to reduce theuntoward effects of metallic device implantation. Such complicationsinclude intimal hyperplasia, thrombosis and lack of native tissueincorporation.

Synthetic materials for stent coverings vary widely, e.g., syntheticmaterials such as Gore-Tex®, polytetrafluoroethylene (PTFE), and aresorbable yarn fabric (U.S. Pat. No. 5,697,969 to Schmitt et al.).Synthetic materials generally are not preferred substrates for cellgrowth.

Biomaterials and biocompatible materials also have been utilized inprostheses. Such attempts include a collagen-coated stent, taught inU.S. Pat. No. 6,187,039 (to Hiles et al.). As well, elastin has beenidentified as a candidate biomaterial for covering a stent (U.S. Pat.No. 5,990,379 (to Gregory)).

In contrast to synthetic materials, collagen-rich biomaterials arebelieved to enhance cell repopulation and therefore reduce the negativeeffects of metallic stents. It is believed that small intestinalsubmucosa (SIS) is particularly effective in this regard.

Bioprosthetic valves combining synthetic and biological materials havealso been studied. For example, U.S. Pat. No. 5,824,06 (to Lemole); U.S.Pat. No. 6,350,282 (to Eberhardt); and U.S. Pat. No. 5,928,281 (toHuynh) teach bioprosthetic heart valves that may employ an aortic valve(comprising animal or patient tissue) sutured to an artificial valveframe.

Some of the above-discussed coverings, while used to prevent untowardeffects, actually exacerbate the effects to some extent. Accordingly, itis desirable to employ a native biomaterial or a biocompatible materialto reduce post-procedural complications.

A mechanically hardier valve graft device is required in certainimplantation sites, such as cardiac, aortic, or other cardiovascularlocations. In order to produce a sturdier bioprosthesis, a plurality oflayers of biomaterial may be used. Suturing is a poor technique forjoining multiple layers of biomaterial. While suturing is adequate tojoin the biomaterial sheets to the metallic frame, the frame-suturedmultiple sheets are not joined on their major surfaces and are thereforesubject to leakage between the layers. Suturing of the major surfaces ofthe biomaterial layers introduces holes into the major surfaces,increasing the risk of conduit fluid leaking through or a tear formingin one of the surfaces.

Heretofore, biomaterials have been attached to bioprosthetic frames,e.g., stents and valves, using conventional suturing techniques. Aswell, the primary methods available for securing prostheses to tissue(or tissue to tissue) involved the use of sutures or staples. However,this approach is disadvantageous from manufacturing and implantationperspectives.

Suturing is time-consuming and labor-intensive. For example, suturing asheet of biomaterial over a stent frame typically is anoperator-dependent process that can take up to two hours for trainedpersonnel. Because suturing is manually performed, there are concernsrelating to manufacturing uniformity and product reliability. As well,suturing entails repeatedly puncturing the biomaterial, creatingnumerous tiny holes that can weaken the biomaterial and potentially leadto leakage and infection after the graft device has been installed.

Moreover, the presence of suture material can enhance the foreign bodyresponse by the host patient, leading to a narrowing of the tubularvessel in which the graft is implanted.

A recent attempt to provide a “sutureless” heart valve prosthesis, U.S.Pat. No. 6,287,339 (to Vazquez, et al.), while providing a valve deviceto be attached to patient tissue without the use of sutures,nevertheless continues to require sutures to secure the active portionof the prosthesis to its abutment structure.

Biocompatible adhesive compounds and photochemical cross-linking agentshave been investigated as alternatives to suturing. For example, fibringlue, a fibrinogen polymer polymerized with thrombin, has been used as atissue sealant and hemostatic agent.

Bioadhesives generally produce rigid, inflexible bond regions that canlead to local biomaterial tears and failure of the graft device. Inaddition, some bioadhesives and photochemical cross-linking agents carryrisk of acute and chronic toxicity and bio-incompatibility.

The invention will become more readily apparent from the followingdetailed description, which proceeds with reference to the drawings, inwhich:

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a top view of a valve graft according to the presentdisclosure.

FIGS. 2-3 are perspective side and axial views, respectively, of the

FIG. 4 is a top view of one embodiment of a valve frame before and aftera distorting force is applied to distort the frame into a flexed state.

FIG. 5 is a top view of the flexed-state valve frame placed on a sheetof biomaterial.

FIG. 6 is a cross-sectional side view of the valve frame and biomaterialtaken through line 6-6 in FIG. 5.

FIG. 7 is a view of the cross-section of FIG. 6, showing folding of theedge of the biomaterial sheet over the wire frame.

FIG. 8 is a view of the cross-section of FIGS. 6-7, showing oneembodiment of sutureless bonding of the edge of the biomaterial sheet tothe first major surface of the sheet at a first bonding locus.

FIG. 9 is a cutaway perspective view diagram of one embodiment of amethod for implanting a valve graft employing a catheter to introducethe folded valve graft to an implantation site in a patient's tubularvessel.

FIG. 10 is a cutaway perspective view diagram showing a valve graftintroduced into a tubular vessel by a catheter.

FIG. 11 is an axial view down the tubular vessel of FIGS. 9-10 fromreference line 11-11, showing the implanted valve graft.

FIGS. 12-13 are cutaway perspective views of the implanted valve graftof FIGS. 10-11, showing unidirectional flow control by the valve graft.

DETAILED DESCRIPTION OF EMBODIMENTS

A valve graft 1 according to the present disclosure is shown in FIGS.1-3. The valve graft generally comprises a valve frame 10 defining avalve frame open area (18 in FIG. 4). The open area is spanned by a pairof valve flaps 12 constructed of a biomaterial, discussed below. Thevalve flaps have positioned therebetween an aperture 14.

The valve frame 10 is preferably a closed loop and is commonlyconstructed of fine-gauge metal (e.g., 0.014 inch diameter), althoughother materials can be effectively employed. For example, the valveframe can alternatively be made of a synthetic material such as TEFLON(polytetrafluoroethylene). As well, the valve frame can be fabricated ofa resorbable or biodegradable composition.

In one embodiment, the valve frame 10 is a memory wire formed into adesired shape. As illustrated herein, the valve frame is rhomboidal,although other shapes can be utilized to effect a variety of valveshapes and dimensions.

Such a shape memory wire frame is known in the art as a frame thatsubstantially returns to its original shape after it is deformed andthen released, as described in U.S. Pat. No. 4,512,338 (to Balko etal.). The alternative compositions disclosed above also can be of amemory character if desired.

The valve flaps 12 span the valve frame open area 18 and aresuturelessly bonded to the valve frame 10. An aperture 14 separates thevalve flaps and serves as a port through which fluid can traverse thevalve graft when in use in a patient's vessel.

The valve flaps 12 preferably are of a collageneous biomaterial and canbe constructed using a variety of collagen-rich biomaterials, e.g., asynthetic collagen matrix or of native tissue-derived, collagen-richbiomaterials such as pericardium, peritoneum, dura mater, fascia andbladder or ureteral acellular matrices.

An exemplary method for making the valve graft described above is shownin FIGS. 4-8. In this method, a valve frame 10 is distorted into aflexed state (FIG. 4). In this flexed state, the ratio of the long axisof the frame to its short axis is increased as compared to the basestate. In the preferred embodiment wherein the frame is composed of amemory material, it should be apparent that the valve frame willtherefore be under tension when flexed.

The valve frame is then placed on a first major surface 22 of a sheet ofbiomaterial 20 (FIGS. 5-6). A cross-section through line 6-6 of FIG. 5,corresponding to the short axis of the valve frame, is shown in FIG. 6.An edge 24 of the biomaterial 20 is folded over the valve frame 10 tocontact the edge with the first major surface 22 of the biomaterial(FIG. 7) and form thereby a first bonding locus 30.

In this embodiment, the biomaterial 20 is a trimmed portion of porcineintestinal submucosa. The intestinal submucosa graft is harvested anddelaminated in accordance with the description in U.S. Pat. Nos.4,956,178 and 4,902,508 (both to Badylak et al.). An intestinalsubmucosa segment is thereby obtained that can be effectively used as abiomaterial sheet as described herein.

Sutureless bonding of the edge 24 of the biomaterial sheet to the firstmajor surface 22 of the sheet is illustrated in FIG. 8. The suturelessbonding can be achieved using thermal bonding or chemical cross-linkingtechniques.

In thermal bonding shown in FIG. 8, the at least first bonding locus 30,in which the edge 24 of the biomaterial 20 is apposed to the first majorsurface 22 thereof, is irradiated with energy 32 sufficiently to heat,denature and fuse together the components of the biomaterial.

The bonding technique is preferably confined to the selected bondingloci, such that the sutureless bonding effectively “spot-welds” thebiomaterial edge to the first major surface of the sheet. Alternatively,the edge can be welded to the first major surface in one or more weldlines.

In irradiating the at least first bonding locus with energy from anenergy source 34, wherein the energy source is an 800 nm diode laser,propagation of laser energy is preferably directed perpendicular to thebiomaterial. The biomaterial, preferably being transparent to the laserlight at the chosen light wavelength, absorbs little energy and hencesustains minimal thermal damage. However, the energy-absorbing materialat the at least first bonding locus absorbs energy and thereby conductsheat to the adjacent biomaterial.

Sutureless bonding using thermal energy preferably creates a weld whileminimizing transfer of heat to surrounding tissues, thereby reducingcollateral thermal damage. The chromophore also can aid in thermalconfinement and thereby reduce denaturation of surrounding tissue.

With sufficient energy irradiation, the biomaterial edge and first majorsurface at the at least first bonding locus are denatured at the proteinlevel. It is believed that the molecules in the biomaterial intertwinewith one another. Upon cooling, the bond site is weld-sealed, whereinthe biomaterial edge and first major surface of the biomaterial arewelded together.

As has been mentioned, the valve frame alternatively can be constructedso as to comprise a biological material amenable to laser fusiontechniques. With such an embodiment, the collagen-rich biomaterial sheetcan be attached to the valve frame by fusion directly thereto, ratherthan folding the sheet around it and fusing the edge to the first majorsurface.

The combination of an energy-absorbing material (i.e., a chromophore,such as indocyanine green (ICG)) and an 800 nm diode laser is thepreferred equipment for sutureless bonding in the method hereindisclosed. The chromophore can be an endogenous or exogenous substance.The at least first bonding locus at the folded-over edge preferablyincludes the chromophore, either by treatment of the biomaterial beforesutureless bonding or by topical application of a chromophore duringsutureless bonding.

Thermal bonding can be accomplished according to either of two models.In a first model as discussed above, a device is remotely employed togenerate heat within the biomaterial. A second thermal bonding modelinvolves contacting a device with the at least first bonding locus fordirect generation of heat at the biomaterial contact site. Such devicesfor contact-heating are known in the art and include a contactthermo-electric transducer.

In a first alternative sutureless bonding model, the biomaterial edgecan be bonded to the first major surface by photo-chemicalcross-linking. In a first embodiment of this technique, methylene blueis introduced to the at least first bonding locus and the region isirradiated with white light or other non-collimated light.

Conventional chemical or photo-crosslinking agents frequently presenttoxicity concerns if introduced into a patient. For this reason, it ispreferable that such agents be avoided or the valve graft well rinsed toremove as much of the agent as possible. Methylene blue is a preferredsubstance for photochemical cross-linking as described above, becausethe dye has been shown to be easily rinsed from collagen-richbiomaterials such as SIS.

The sutureless bonding technique used can vary according to desiredlocus size, biomaterial, speed, cost, and procedural considerations. Inall cases, however, it is apparent that the disclosed method avoids theuse of sutures to attach the biomaterial to the prosthesis frame.

Sutureless bonding as disclosed herein possesses a satisfactory bondstrength to permit the valve graft to be implanted into a patient'stubular vessel without increasing the risk of bond failure over that ofconventional sutured attachment schemes. As has been mentioned, thepresence of sutures at an implantation site increases the probability ofpost-procedure complications, such as foreign body reaction,thrombogenesis, leakage and reflux of fluid. Use of the suturelessbonding method therefore produces a valve graft more readily received bya patient's body.

The present method results in thermal fusion of the biomaterial togenerate a strong bond. As well, the resulting valve graft provides ahigh affinity, migratory, and integrative capability for host cell andtissue ingrowth. The bioprosthesis also prevents fluid leakage whileretaining a soft, pliable character. Employment of a biomaterial sheathand avoidance of sutures provide a non-carcinogenic valve stent thatgreatly minimizes calcification and foreign body reactions.

An aperture 14 is formed in the biomaterial sheet 20, creating thebidentate valve graft shown herein. The width of the aperture can bevaried to control the flexibility of the valve and the maximum flow ratethrough the valve.

FIGS. 9-10 are diagrams of one embodiment of a method for implanting avalve graft 1 at an implantation site 40 in a patient's tubular vessel50. The valve graft 1 first is folded along one axis (i.e., alongreference line A-A in FIG. 1), bringing proximate the distal corners ofthe frame.

The biomaterial sheet typically is stretched thereby and preferablycurves below the short axis and toward the distal corners, taking on asaddle-like shape. Owing to both the composition of the valve frame andthe tensile strength of the biomaterial, tension on the biomaterial isnot so great as to tear the biomaterial or to pull open the aperture.

A catheter 60 is preferably employed to introduce the folded valve graftto the implantation site. The valve graft 1 is sufficiently tightlyfolded to permit the valve graft to be placed within the catheter 60.This fitment is generally achieved by bringing the distal corners closerand also compressing the frame along the fold axis. The resultant foldedvalve graft has a high aspect ratio relative to its relaxed orientation(i.e., as shown in FIG. 9).

The catheter 60 is then maneuvered to position the distal tip thereof atthe implantation site 40, such as in a vein 50. The tightly-folded valvegraft is introduced into the vein or other tubular vessel by deploymentfrom the distal tip of the catheter 60, as shown in FIG. 10. Suchrelease can be achieved by pushing the valve graft from inside thecatheter with a ramrod-type element 62, such as a guidewire.

Upon release from the catheter, the valve graft will tend to spring backto its original conformation, limited by the walls of the tubular vessel(FIGS. 10-11, with the valve aperture shown open). This expandingtendency is due to the shape memory material of which the valve frame isconstructed.

The valve graft will remain at the implantation site in a folded state,though not so tightly folded as in FIG. 9. Over time, native tissueovergrowth occurs, further anchoring the valve graft in place.

A collagen-rich biomaterial sheet can serve as a layer(s) (single ormultiple sheets) applied to a supporting structure (e.g., valve frame)to control fluid flow direction through the conduit while preventingleakage out of the conduit. Such valve grafts might be used, forexample, in the cardiovascular system (blood vessels), gastrointestinaltract, urinary tract, and trachea

FIGS. 12-13 show simplified views of the implanted valve graft of FIGS.10-11, illustrating unidirectional flow control via valve action. Forpurposes of explanation, it will be assumed that a valve graft has beenimplanted in a vein of a patient.

It should be noted that the flaps 12 or leaflets of the valve graft 1have a flexible character imparted by the composition of the biomaterialsheet 20. The flaps 12 therefore can be flexed or bowed by the force ofthe incident fluid. Such pliant or elastic property is known in the artfor “natural tissue” valves, as opposed to mechanical valves.

In FIG. 12, anterograde blood flow in the vein 50 is occurring,consistent with normal circulation, i.e., from right to left. Pressureon the upstream surface of the valve graft flaps 12 by the blood (solidarrow) causes the flaps 12 to be bowed toward the walls of the vein 50.The valve graft aperture 14 is opened thereby, permitting the blood toflow through the valve graft 1 and further downstream (solid arrow)through the vein 50.

In retrograde blood flow to the valve (solid arrow, FIG. 13), bloodfills and is trapped in the “dead-end” regions between the valve graftflaps 12 and the vein wall 50. This phenomenon, coupled with thecontinuing-fluid pressure on the flaps 12 caused by physiological bloodflow, causes blood to contact and press on the downstream surface of thevalve graft flaps, flexing them inward and away from the vessel walls50. By bowing the flaps inward, the valve graft aperture 14 iseffectively closed and retrograde flow through the valve graft issubstantially prevented (dashed arrow).

A valve graft preferably is constructed in which the aperture issubstantially closed when the valve graft is in a resting-stateconformation (i.e., its state when implanted in a vessel having no fluidflow). Such construction is dependent on the size, shape, and dimensionsof the valve frame, the presence and degree of tension that can beapplied to the biomaterial sheet during valve graft fabrication, and thedimensions and orientation of the aperture.

In another alternative valve graft, the aperture can be designed toincompletely close or to substantially narrow in the face of retrogradeflow, depending on the particular configuration and dimensions of theimplanted valve graft. If a partial retrograde flow is desired, forexample, the aperture dimensions can be chosen to prevent completeclosure of the aperture in an in situ implantation.

Implantation of a valve graft according to the present disclosureprovides several benefits over prior art prostheses. Collagen and SISare known to provide a matrix that encourages native cell repopulationand may ultimately enhance tissue repair and regeneration as well asintegration of implanted supporting structure materials.

One advantage of the disclosed method for making a valve graft is thatthermal bonding, and especially laser fusion of the biomaterial edge tothe first major surface is a rapid technique that yields water-tightbonds. As well, laser fusion has the capability of attaching multiplebiomaterial sheets at numerous locations on their major surfaces,reducing the chance of leakage between the biomaterial sheets.

Heretofore, laser fusion has not gained widespread acceptance forbonding approximated tissue edges, largely because of weak bondstrength. However, laser fusion of collagen-rich biomaterials asdescribed herein resulted in strong tissue bonds. Further, collagen-richbiomaterials have been observed to readily incorporate chromophores suchas ICG, further enhancing the efficacy of laser fusion in the presentinvention.

Another advantage of the present valve graft over prior art prosthesesis that the use of sutures is obviated in the present invention. Therisk of a foreign body response is therefore substantially mitigated.

A further advantage is that a valve graft as disclosed herein andconstructed with collageneous biomaterial flaps will retain theexcellent bio-active properties of small intestinal submucosa graft withgreatly reduced risk of cytotoxicity and foreign body reactions. Thesutureless bonding welds provide sufficient mechanical and structuralstrength to enable the valve graft to be employed in medical proceduresand to function acceptably in situ.

A person skilled in the art will be able to practice the presentinvention in view of the description present in this document, which isto be taken as a whole. Numerous details have been set forth in order toprovide a more thorough understanding of the invention. In otherinstances, well-known features have not been described in detail inorder not to obscure unnecessarily the invention.

While the invention has been disclosed in its preferred form, thespecific embodiments presented herein are not to be considered in alimiting sense. Indeed, it should be readily apparent to those skilledin the art in view of the present description that the invention can bemodified in numerous ways. The inventor regards the subject matter ofthe invention to include all combinations and sub-combinations of thevarious elements, features, functions and/or properties disclosedherein.

1. (Canceled)
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 3. (Canceled)
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 5. (Canceled) 6.(Canceled)
 7. (Canceled)
 8. (Canceled)
 9. (Canceled)
 10. A method forproducing a sutureless valve graft suitable for physiologicalimplantation, comprising: positioning a flexible valve frame defining anopen area on a first major surface of a biomaterial sheet having aperipheral edge, said positioning serving to approximate the valve frameand the peripheral edge of the biomaterial sheet to form an at leastfirst bonding locus; and suturelessly bonding the biomaterial to thevalve frame at the at least first bonding locus.
 11. The method of claim10, wherein positioning comprises: positioning the valve frame on thefirst major surface-of the biomaterial sheet; and folding the edge ofthe biomaterial sheet over the valve frame so that the edge of thebiomaterial sheet is contacted with the first major surface of thebiomaterial sheet.
 12. The method of claim 10, wherein suturelesslybonding comprises suturelessly bonding the edge of the biomaterial sheetdirectly to the valve frame.
 13. The method of claim 10, furthercomprising: applying a distorting force to the valve frame to distortthe valve frame into a flexed state prior to positioning the valveframe; and releasing the distorting force after suturelessly bonding.14. The method of claim 10, wherein the biomaterial sheet consistsessentially of small intestine submucosa.
 15. The method of claim 10,wherein suturelessly bonding comprises irradiating the at least firstbonding locus with energy sufficient to at least partially fuse theportion of the approximated biomaterial sheet to attach the biomaterialto the valve frame at the at least first bonding locus.
 16. The methodof claim 15, wherein irradiating the at least first bonding locus withenergy comprises irradiating the at least first bonding locus withlight.
 17. The method of claim 16, wherein irradiating the at leastfirst bonding locus with energy comprises irradiating the at least firstbonding locus with light generated by a laser.
 18. The method of claim17, wherein irradiating the at least first bonding locus with energycomprises irradiating the at least first bonding locus with light havinga wavelength of about 800 nm.
 19. The method of claim 18, furthercomprising introducing a chromophore that is energy-absorptive at about800 nm.
 20. The method of claim 10, further comprising introducing aphoto-chemical crosslinking agent.
 21. The method of claim 20, whereinsaid photo-chemical crosslinking agent is methylene blue.
 22. The methodof claim 21, wherein irradiating the at least first bonding locus withenergy comprises irradiating the at least first bonding locus with whitelight.
 23. The method of claim 21, wherein irradiating the at leastfirst bonding locus with energy comprises irradiating the at least firstbonding locus with ultraviolet light.
 24. The method of claim 15,wherein irradiating the at least first bonding locus with energycomprises irradiating the at least first bonding locus withradio-frequency energy.
 25. The method of claim 15, wherein irradiatingthe at least first bonding locus with energy comprises irradiating theat least first bonding locus with ultrasound energy.
 26. The method ofclaim 10, further comprising creating an aperture across a short axis ofthe biomaterial sheet.
 27. The method of claim 10, further comprisingdehydrating the biomaterial prior to suturelessly bonding; andrehydrating the biomaterial after suturelessly bonding.
 28. The methodof claim 10, further comprising securing the valve frame in the flexedstate by attaching a diametric suture, wherein releasing the distortingforce comprises removing the diametric suture.
 29. A method forsuturelessly attaching a collagen-rich biomaterial sheet to a prosthesisframe element, comprising: approximating a portion of the biomaterialsheet to the prosthesis frame element to define an at least firstbonding locus; and irradiating the at least first bonding locus withenergy from an energy-generating source, said energy sufficient to atleast partially fuse the portion of the approximated biomaterial sheet.30. The method of claim 29, wherein irradiating the at least firstbonding locus with energy from an energy-generating source comprisesirradiating the at least first bonding locus with energy from aradio-frequency device.
 31. The method of claim 29, wherein irradiatingthe at least first bonding locus with energy from an energy-generatingsource comprises irradiating the at least first bonding locus withenergy from an ultrasound device.
 32. The method of claim 29, whereinirradiating the at least first bonding locus with energy from anenergy-generating source comprises irradiating the at least firstbonding locus with light energy from a laser.
 33. The method of claim32, wherein said laser emits light having a wavelength of about 800 nm.34. The method of claim 32, further comprising introducing achromophore.
 35. The method of claim 34, wherein said chromophore isindocyanine green.
 36. The method of claim 29, wherein irradiating theat least first bonding locus with energy from an energy-generatingsource comprises contacting the at least first bonding locus with acontact thermo-electric transducer.
 37. The method of claim 29, furthercomprising dehydrating the biomaterial prior to bonding; and rehydratingthe biomaterial after bonding.
 38. The method of claim 29, wherein theprosthesis frame element comprises a synthetic material.
 39. The methodof claim 29, wherein the prosthesis frame element comprises abiomaterial.
 40. The method of claim 29, wherein the biomaterialconsists essentially of collagen.
 41. The method of claim 29, whereinthe biomaterial substantially comprises small intestine submucosa. 42.(Canceled)
 43. (Canceled)
 44. (Canceled)
 45. (Canceled)
 46. The methodof claim 10 wherein the biomaterial sheet comprises collagen.
 47. Amethod for securing a biomaterial sheet to a stent frame, comprising:approximating a portion of the biomaterial sheet to the stent frame todefine an at least first bonding locus; irradiating the at least firstbonding locus with energy from an energy-generating source, said energysufficient to at least partially fuse the portion of the approximatedbiomaterial sheet.
 48. The method of claim 47 wherein the energy isoptical energy.
 49. The method of claim 48 wherein irradiating theoptical energy is laser optical energy.
 50. The method of claim 48wherein the optical energy has a wavelength of about 800 nm.
 51. Themethod of claim 50, further comprising introducing a chromophore that isenergy-absorptive at about 800 nm.
 52. The method of claim 48, furthercomprising introducing a photo-chemical crosslinking agent.
 53. Themethod of claim 48 wherein the optical energy is white light.
 54. Themethod of claim 48 wherein the optical energy is ultraviolet light. 55.The method of claim 47 wherein the energy is radio-frequency energy. 56.The method of claim 47 wherein the energy is ultrasound energy.
 57. Themethod of claim 47, further comprising: at least partially dehydratingthe biomaterial prior to irradiating; and rehydrating the at leastpartially dehydrated biomaterial after irradiating.